The present invention relates to new acylamino acid derivatives with valuable pharmacological properties, especially properties favorably affecting nitrogen metabolism, to the use of these acylamino acid derivatives as pharmaceuticals and dietetics, especially for the treatment and prophylaxis of, for example, disturbances of nitrogen metabolism caused by liver and/or kidney damage in relatively large mammals, especially humans, to pharmaceuticals and dietetics which contain acylamino acid derivatives as active ingredients, and to the preparation of the acylamino acid derivatives.
It is known that the corresponding .alpha.-keto analogs of essential amino acids are possible substitutes for the essential amino acids. After enzymatic transamination, the .alpha.-keto analogs are, with a few exceptions, available as building blocks for proteins in the body (J. H. Close, N. Engl. J. Med. 290 (1974), pp. 663-667).
Leucine and its .alpha.-keto analog 4-methyl-2-oxovaleric acid (.alpha.-ketoleucine) play a special part in protein synthesis because the modes of action of the two substrates complement each other synergistically. On the one hand, protein synthesis is stimulated by leucine, and on the other hand, protein breakdown is inhibited by .alpha.-ketoleucine (M. E. Tischler, M. Desantels, A. L. Goldberg, J. Biol.-Chem. 257 (1982), pp. 1613-1621).
Furthermore, nitrogen is consumed in the synthesis of .alpha.-amino acids from their corresponding .alpha.-keto analogs in the body, which leads additionally to a reduction in the amount of nitrogen compounds excreted in the urine.
This knowledge has been applied by utilizing the effects of .alpha.-keto and .alpha.-amino acids in a wide variety of metabolic situations, especially in catabolic states as occur in connection with hepatic and renal insufficiencies, trauma, sepsis and fasting states.
Compositions which contain .alpha.-amino carboxylic acids and .alpha.-keto analogs of amino carboxylic acids are disclosed, for example, in French Patent Application No. FR 2,556,593 or are already marketed in the form of preparations for oral administration, such as, for example, the commercial product ULTRAMINE (manufactured by Pfrimmer).
Although these products have been used successfully in therapy, there are still various problems associated both with their manufacture and with their oral and parenteral use. Thus, for example, when administered orally, these amino acids and .alpha.-keto analogs are, unfortunately, not utilized optimally because of the absorption behavior.
When administered parenterally as described, for example, for leucine and ketoleucine by G. Francois et al. (Clin. Nutr., 3 (1984), pp. 99-101), the advantageous effect of a reduction in nitrogen excretion can only be achieved if substrates of carbohydrate metabolism are administered concurrently. However, infusion solutions which are manufactured to contain substrates of carbohydrate metabolism in addition to amino acids and their .alpha.-keto analogs have the disadvantage that when reducing sugars such as, for example, glucose are used, Maillard products may form in completely assembled infusion solutions either during the necessary heat sterilization or during storage.